There is ample evidence suggesting that immunologic factors affect the course of human malignant melanoma. The objective of this proposal is to demonstrate, isolate and characterize the cell surface antigens of melanoma cells which are responsible for this immune response. To this end, we have identified a significant number of autologous reactions between antibody in patients' sera directed towards their own cultured melanoma cells. These results will enable us to examine antibody-cell surface interactions uncomplicated by allogeneic differences. The techniques to be used will be modifications of those which have been used for the detection and study of transplantation and other cell-surface antigens on mammalian cells. By using a variety of radiolabeling techniques we intend to label a spectrum of cell surface components. After solubilization, the nature of the components reacting with autologous antibody will be studied using a double-antibody technique. By examination of these specific precipitates we will gain information concerning the specificity of the autologous immune response and on the biochemical nature of the reactive antigens. Antigens will also be isolated and fractionated by standard biochemical techniques in which the fractionation is followed by inhibition of the appropriate serological analysis.